Method, compositions and devices for administration of naked polynucleotides which encode antigens and immunostimulatory

Abstract

This invention relates to methods for administering antigens and immunostimulatory peptides to a mammalian host by the introduction of one or more naked polynucleotides to operatively encode for the antigens and immunostimulatory peptides, preferably by non-invasive means.

Claims

1. A method for introducing an antigen to a vertebrate host comprising:

administering a naked polynucleotide into the skin of the host at a depth no deeper than the subcutaneous layer of the skin to introduce the polynucleotide into antigen presenting cells present in the skin;

wherein the naked polynucleotide operatively encodes for the antigen and is naked in that the polynucleotide is not complexed to any colloidal material which interferes with uptake of the polynucleotide by antigen presenting cells; and,

wherein the antigen is expressed in the antigen presenting cells to stimulate a host Th1 type immune response.

2. The method according to claim 1 wherein the route of administration of the naked polynucleotide comprises transdermal transmission.

3. The method according to claim 1 wherein the route of administration comprises application of the naked polynucleotide in a pharmaceutically acceptable topical composition to the epidermis of the host, and coadministration of a chemical irritant capable of provoking an immune response to the irritant to attract additional antigen presenting cells to the site of irritation for uptake of the naked polynucleotide.

4. The method according to claim 1 wherein the naked polynucleotide is administered by use of means to mechanically irritate the epidermis of the host to attract additional antigen presenting cells for uptake and expression of the naked polynucleotide.

5. The method according to claim 1 wherein the route of administration comprises intradermal or subcutaneous injection.

6. The method according to claim 2 wherein the transmission is achieved by use of a iontophoresis patch.

7. The method according to claim 1 wherein up to 200 operatively encoding naked polynucleotides are administered in a mixture.

8. The method according to claim 7 wherein at least some of the polynucleotides in the mixture separately and operatively encode for different antigens.

9. The method according to claim 1 wherein the naked polynucleotide is selected from the group of molecules consisting of DNA, RNA and cDNA.

10. The method according to claim 7 further comprising administering an immunostimulatory peptide to the host.

11. A composition comprising (a) at least one naked polynucleotide which is susceptible to uptake by antigen presenting cells, is naked in that the polynucleotide is not complexed to any colloidal material which interferes with uptake of the polynucleotide by antigen presenting cells and which operatively encodes for an antigen or immunostimulatory peptide, (b) a pharmaceutically acceptable carrier containing the naked polynucleotide, and (c) a keratinolytic agent capable of irritating a mammalian epidermis or mucosal epithelia to induce an immune response and attracting additional antigen presenting cells for uptake and expression of the naked polynucleotide to stimulate a host Th1 type immune response.

12. The method according to claim 3 wherein the chemical irritant consists essentially of a keratinolytic agent.

13. The method according to claim 1 wherein the Th1 type immune response is stimulated for response to an antigen already present in, or administered separately to, the host.

14. The method according to claim 10 wherein the immunostimulatory peptide is expressed from the naked polynucleotide.

15. The method according to claim 10 wherein the immunostimulatory peptide is selected from the group of peptides consisting of antigens, hormones, adjuvants, cytokines and growth factors.

16. A method for introducing an antigen to a vertebrate host comprising:

administering a naked polynucleotide in a pharmaceutically acceptable carrier into a mucosal tissue of the host at a depth no deeper than the epithelial layer of the mucosa to introduce the naked polynucleotide into the antigen presenting cells present in the mucosa;

wherein the naked polynucleotide operatively encodes for the antigen and is naked in that the polynucleotide is not complexed to any colloidal material which interferes with uptake of the polynucleotide by antigen presenting cells; and,

wherein the antigen is expressed in the antigen presenting cells to stimulate a host Th1 type immune response.

17. The method according to claim 16 wherein the route of administration comprises application of the naked polynucleotide in a pharmaceutically acceptable topical composition to the mucosal epithelia of the host and coadministration of a chemical irritant to attract additional antigen presenting cells for uptake and expression of the naked polynucleotide.

18. The method according to claim 16 wherein the naked polynucleotide is administered by use of means to mechanically irritate the mucosal epithelia of the host to attract additional antigen presenting cells for uptake and expression of the naked polynucleotide.

19. The method according to claim 16 wherein up to 200 operatively encoding naked polynucleotides are administered in a mixture.

20. The method according to claim 19 wherein at least some of the polynucleotides in the mixture separately and operatively encode for different antigens.

21. The method according to claim 16 wherein the naked polynucleotide is selected from the group of polynucleotides consisting of DNA, RNA and cDNA.

22. The method according to claim 16 wherein the immunostimulatory peptide is selected from the group of peptides consisting of antigens, cytokines, adjuvants, hormones and growth factors.

23. The method according to claim 16 wherein the Th1 type immune response is stimulated for response to an antigen already present in, or administered separately to, the host.